In a report by Kim and Chauhan [Internat. J. Pharm, 353, 204 (2008)], the authors noted that (1) most treatments of ocular diseases are still based on topical applications of eye drops to the surface of the eye in spite of the many novel approaches which have been developed over the past two decades; (2) after application of an eye drop, the drug solution mixes with tear fluid and then within five minutes, the majority of the drug (95-99%) is eliminated by tear drainage and conjunctival uptake—in order to maintain therapeutic levels of drug concentration, frequent instillation of drops with large drug loadings are required which is inconvenient to the patient with possible side effects; (3) to overcome the drawbacks of the drops, several ophthalmic drug delivery systems have been proposed, such as suspension of nanoparticles, liposomes, ocular inserts (e.g., collagen shields and Ocusert®) and therapeutic contact lenses; and (4) on instillation of medicated contact lens in the eye, the drug diffuses through the lens matrix into the thin tear film named post-lens tear film (POLTF) trapped between the lens and cornea, thus permitting the drug to have a residence time of about 30 minutes in the eye, which increases the drug bioavailability by about an order of magnitude longer than the drops.
In an earlier review by LaBaurlais and coworkers [Progress in Retinal and Eye Research, 17, 33 (1998)] intended to accelerate the transport of methylprednisolone to the eye tissues, the authors used transscleral column-controlled iontophoresis with the platinum electrode in contact with the drug solution in the cup-shaped reservoir in a silicone applicator, placed on the intact rabbit conjunctiva and sclera adjacent to the limbus while placing the positive electrode on the rabbit ear.
In concert with the above-noted technical literature in ocular drug delivery, U.S. Patent Application, Serial No. 2004/0071761 singled out the topical application of drug as a facile route of administration in spite of certain drawbacks associated primarily with drug loss through tear drainage and conjunctival uptake. This application also claimed a pharmaceutical formulation for the treatment of posterior ocular conditions comprising an effective amount of a therapeutic compound and at least one means of enhancing the transport of the therapeutic compound across the sclera of an eye toward and into at least one of an intermediate and posterior portions of the eye and means for prolonging the residence time of the therapeutic compound within the intermediate and posterior portions of the eye. Towards achieving this, the inventor described the preferred use of a gauze pad having the pharmaceutical compound impregnated therein. Alternatively, the inventor described the use of a patch, a sponge, a hydrogel, a porous ceramic or silicone-based membrane as substitutes for the gauze.
Analysis of the aforementioned discussion of the different approaches to ocular drug delivery indicate that (1) topical drug application is the most non-invasive mode of administration; (2) traditional use of eye drops is least effective for a timely delivery of therapeutic drugs; (3) a drug carrier of well-defined geometry that adheres to the sclera and localizes the drug availability to the specific interface between the carrier and the sclera; (4) the lack of an easy-to-deploy, patient-friendly topical drug delivery system; (5) rapid release of the therapeutic agent in high concentrations is most effective; and (6) iontophoresis can be used to accelerate the release rate of the drug from a properly designed drug release system for topical application. This prompted exploring the study subject of this invention, which deals primarily with a composite construct comprising an hydrophilic microcellular foam as a drug carrier adjoined with flexible hydrophobic barrier film to facilitate handling and directing the drug transport. The release rate of the drug can be accelerated through incorporating the construct in an iontophoretic transscleral delivery system.